Objective of the proposed investigation is to establish (1) the role of Na-K-ATPase in the active transport of sodium by the renal tubule of the normal kidney, and (2) to evaluate its significance in certain pathological conditions characterized by abnormal renal sodium metabolism. (1) Whereas previous work by applicant indicates that Na-K-ATPase is probably operative in the adaptation to long-term changes in tubular sodium transport, its role in the rapid adjustments of sodium reabsorption in response to acute changes in filtered sodium is virtually unknown. The proposed investigation will address itself to the elucidation of this question by studying effects of acute changes in filtered sodium on renal microsomal Na-K-ATPase specific activity and kinetic properties, and effect of short-term infusion of two-enzyme inhibitors, Oligomycin and Vilinomycin, on renal sodium handling in the rat. The mechanism of enzyme stimulation will be evaluated by the simultaneous administration with the procedure found most effective in increasing Na-K-ATPase, of Actinomycin D and Cycloheximide, which act at different steps in the sequence of events leading to protein synthesis de novo. (2) Thyroid deficiency is accompanied by widespread renal functional alterations whose common denominator appears to be a defect in the tubular reabsorption of sodium. In the second part of this proposal we will study the relation of Na-K-ATPase to the renal functional defects in hypothyroidism with emphasis on the renal concentrating and diluting abnormalities found in this condition.